Development and Testing of New Screening Method for Keratan Sulfate in Mucopolysaccharidosis IVA

Shunji Tomatsu, Kazuo Okamura, Takeshi Taketani, Koji O. Orii, Tatsuo Nishioka, Monica A. Gutierrez, Susana Velez-Castrillon, Angela A. Fachel, Jeffrey H. Grubb, Alan Cooper, Margaret Thornley, Ed Wraith, Luis A. Barrera, Roberto Giugliani, Ida V. Schwartz, Gudrun Schulze Frenking, Michael Beck, Susanne G. Kircher, Eduard Paschke, Seiji YamaguchiKurt Ullrich, Koji Isogai, Yasuyuki Suzuki, Tadao Orii, Naomi Kondo, Michael Creer, Akihiko Noguchi

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Mucopolysaccharidosis IVA (MPS IVA), a progressive lysosomal storage disease, causes skeletal dysplasia through excessive storage of keratan sulfate (KS). We developed an ELISA-sandwich assay that used a MAb specific to KS. Forty-five blood and 59 urine specimens from MPS IVA patients (ages 1-65 y) were analyzed to determine whether KS concentration is a suitable marker for early diagnosis and longitudinal assessment of disease severity. Blood specimens were obtained from patients categorized as phenotypically severe (n = 36) and milder (n = 9). Urine specimens were also analyzed from patients categorized as severe (n = 56) and milder (n = 12), respectively. Blood KS levels (101-1525 ng/mL) in MPS IVA patients were two to eight times higher than those in age-matched controls (15-323 ng/mL). It was found that blood KS level varied with age and clinical severity. Blood KS levels in both MPS IVA and controls peaked between 5 and 10 y of age (mean, 776 versus 234 ng/mL, respectively). Blood levels in severe MPS IVA were 1.5 times higher than in the milder form. In contrast to blood, urine KS levels in both MPS IVA and controls peaked between 1 and 5 y (15.3 versus 0.26 mg/g creatinine), and thereafter declined with age. Urine KS level also varied with age and clinical severity, and the severe MPS IVA phenotype was associated with 6.7 times greater urine KS excretion than the milder one. These findings indicate that the new assay for blood or urine KS may be suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.

Original languageEnglish (US)
Pages (from-to)592-597
Number of pages6
JournalPediatric Research
Volume55
Issue number4
DOIs
StatePublished - Apr 2004

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

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